Disruption of Nrxn1α within excitatory forebrain circuits drives value-based dysfunction.

Goal-directed behaviors are essential for normal function and significantly impaired in neuropsychiatric disorders. Despite extensive associations between genetic mutations and these disorders, the molecular contributions to goal-directed dysfunction remain unclear. We examined mice with constitutive and brain region-specific mutations in Neurexin1α, a neuropsychiatric disease-associated synaptic molecule, in value-based choice paradigms. We found Neurexin1α knockouts exhibited reduced selection of beneficial outcomes and impaired avoidance of costlier options. Reinforcement modeling suggested that this was driven by deficits in updating and representation of value. Disruption of Neurexin1α within telencephalic excitatory projection neurons, but not thalamic neurons, recapitulated choice abnormalities of global Neurexin1α knockouts. Furthermore, this selective forebrain excitatory knockout of Neurexin1α perturbed value-modulated neural signals within striatum, a central node in feedback-based reinforcement learning. By relating deficits in value-based decision-making to region-specific Nrxn1α disruption and changes in value-modulated neural activity, we reveal potential neural substrates for the pathophysiology of neuropsychiatric disease-associated cognitive dysfunction.

The spectrum of facial palsy: The MEEI facial palsy photo and video standard set.

OBJECTIVES: Facial palsy causes variable facial disfigurement ranging from subtle asymmetry to crippling deformity. There is no existing standard database to serve as a resource for facial palsy education and research. We present a standardized set of facial photographs and videos representing the entire spectrum of flaccid and nonflaccid (aberrantly regenerated or synkinetic) facial palsy. To demonstrate the utility of the dataset, we describe the relationship between level of facial function and perceived emotion expression as determined by an automated emotion detection, machine learning-based algorithm. METHODS: Photographs and videos of patients with both flaccid and nonflaccid facial palsy were prospectively gathered. The degree of facial palsy was quantified using eFACE, House-Brackmann, and Sunnybrook scales. Perceived emotion during a standard video of facial movements was determined using an automated, machine learning algorithm. RESULTS: Sixty participants were enrolled and categorized by eFACE score across the range of facial function. Patients with complete flaccid facial palsy (eFACE <60) had a significant loss of perceived joy compared to the nonflaccid and normal groups. Additionally, patients with only moderate flaccid and nonflaccid facial palsy had a significant increase in perceived negative emotion (contempt) when compared to the normal group. CONCLUSION: We provide this open-source database to assist in comparing current and future scales of facial function as well as facilitate comprehensive investigation of the entire spectrum of facial palsy. The automated machine learning-based algorithm detected negative emotions at moderate levels of facial palsy and suggested a threshold severity of flaccid facial palsy beyond which joy was not perceived. LEVEL OF EVIDENCE: NA Laryngoscope, 130:32-37, 2020.

An International Collaborative Standardizing Patient-Centered Outcome Measures in Pediatric Facial Palsy.

IMPORTANCE: Standardization of outcome measurement using a patient-centered approach in pediatric facial palsy may help aid the advancement of clinical care in this population. OBJECTIVE: To develop a standardized outcome measurement set for pediatric patients with facial palsy through an international multidisciplinary group of health care professionals, researchers, and patients and patient representatives. DESIGN, SETTING, AND PARTICIPANTS: A working group of health care experts and patient representatives (n = 21), along with external reviewers, participated in the study. Seven teleconferences were conducted over a 9-month period between December 3, 2016, and September 23, 2017, under the guidance of the International Consortium for Health Outcomes Measurement, each followed with a 2-round Delphi process to develop consensus. This process defined the scope, outcome domains, measurement tools, time points for measurements, and case-mix variables deemed essential to a standardized outcome measurement set. Each teleconference was informed by a comprehensive review of literature and through communication with patient advisory groups. Literature review of PubMed was conducted for research published between January 1, 1981, and November 30, 2016. MAIN OUTCOMES AND MEASURES: The study aim was to develop the outcomes and measures relevant to children with facial palsy as opposed to studying the effect of a particular intervention. RESULTS: The 21 members of the working group included pediatric facial palsy experts from 9 countries. The literature review identified 1628 papers, of which 395 (24.3%) were screened and 83 (5.1%) were included for qualitative evaluation. A standard set of outcome measurements was designed by the working group to allow the recording of outcomes after all forms of surgical and nonsurgical facial palsy treatments among pediatric patients of all ages. Unilateral or bilateral, congenital or acquired, permanent or temporary, and single-territory or multiterritory facial palsy can be evaluated using this standard set. Functional, appearance, psychosocial, and administrative outcomes were selected for inclusion. Clinimetric and psychometric outcome measurement tools (clinician-, patient-, and patient proxy-reported) and time points for measuring patient outcomes were established. Eighty-six independent reviews of the standard set were completed, and 34 (85%) of the 40 patients and patient representatives and 44 (96%) of the 46 health care professionals who participated in the reviews agreed that the standard set would capture the outcomes that matter most to children with facial palsy. CONCLUSIONS AND RELEVANCE: This international collaborative study produced a free standardized set of outcome measures for evaluating the quality of care provided to pediatric patients with facial palsy, allowing benchmarking of clinicians, comparison of treatment pathways, and introduction of value-based reimbursement strategies in the field of pediatric facial palsy. LEVEL OF EVIDENCE: NA.

Patient experience in nerve-to-masseter-driven smile reanimation.

INTRODUCTION: The nerve-to-masseter is one of the most frequently used neural sources in smile reanimation surgery. Very little information has been reported on patient experience with regard to reanimated smile usage and sequelae following transfer. The aim of this study was to quantify patient perception of nerve-to-masseter use in smile reanimation surgery. METHODS: An online questionnaire was developed based on the clinical expertise of our team, patient interviews, and existing questionnaires of facial palsy-related quality of life and temporomandibular joint dysfunction. All patients treated with nerve-to-masseter-driven smile reanimation surgery, both nerve transfers and muscle transplantations, between 2007 and 2016 with a valid email address were invited to participate. RESULTS: Of 171 operated patients, 122 with a valid email address were invited to participate. Seventy-one patients responded (63.4% female, mean age 51.1 years) after a median follow-up of 3.8 years. A voluntary smile while biting down at least "most of the time" was reported by 83.1% of patients; 46.5% reported ability to smile on the affected side without bite. A "normal" or "almost normal" spontaneous smile was reported in 23.9% of patients. A total of 18.3% of patients self-reported masseter muscle atrophy, and 1.4-14.1% reported temporomandibular joint dysfunction. Forty-one patients (57.7%) reported prandial movement of the face at least "most of the time," with 9 patients (12.7%) considering this bothersome. CONCLUSION: Patients report good voluntary smiling ability following nerve-to-masseter-driven smile reanimation surgery, with low rates of sequelae.

Facial Rehabilitation: Evaluation and Treatment Strategies for the Patient with Facial Palsy.

This article describes the most widely used clinician-graded and patient-reported outcome measures, and describes facial rehabilitation strategies for acute and chronic facial palsy, and rehabilitation following dynamic facial reanimation surgery. The multimodality rehabilitation of the facial palsy patient is determined by the extent of facial nerve injury, specific functional deficits, the presence of synkinesis, and the patient's individual goals. Appropriate intervention, including patient education, soft tissue mobilization, neuromuscular reeducation, and chemodenervation, decreases facial tension and improves facial muscle motor control, physical function, facial expression, and quality of life.

Emerging vs Time-Tested Methods of Facial Grading Among Patients With Facial Paralysis.

IMPORTANCE: Most rehabilitation specialists and many facial reanimation surgeons use the Sunnybrook Facial Grading System (FGS) to measure and detect changes in facial function. The eFACE, an electronic and digitally graded facial measurement scale, was recently created to provide similar information to the Sunnybrook FGS, but with scaling uniformity across all categories of facial function, graphical outputs, and easy-to-use visual analog scales. OBJECTIVES: To establish the correlation between the scores on the eFACE and the Sunnybrook FGS among patients with facial paralysis and to compare the reliability of the 2 scales. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of medical records identified 109 patients who were evaluated at a facial nerve center by physical therapists using the eFACE and the Sunnybrook FGS on the same day, between November 1, 2014, and May 31, 2015. The level of facial function predicted using the 2 scales was compared to study correlation between the scales. Data analysis was conducted from June 1 to September 1, 2015. MAIN OUTCOMES AND MEASURES: Correlation between the Sunnybrook FGS and the eFACE grading scale. METHODS: Two independent physical therapists evaluated patients using both the eFACE and the Sunnybrook FGS. Scores were compared and the Spearman rank correlation coefficient was calculated between the total scores and each of the 3 subscores, including static, dynamic, and synkinesis scores. The total Sunnybrook FGS synkinesis score (worst score, 15; perfect score, 0) and static score (worst score, 20; perfect score, 0) were normalized to a 100-point scale with the eFACE (perfect score, 100; worst score, 1). RESULTS: eFACE scores ranged from 48 to 100, and Sunnybrook FGS scores ranged from 0 to 100. Among 109 patients, there was a moderately strong correlation between eFACE and Sunnybrook FGS scores in both total and subcategory scores. The Spearman rank correlation coefficient of the total eFACE and Sunnybrook FGS was 0.75 (r < 0.0001). For the static scores, the correlation coefficient was -0.71 (r < 0.0001). The correlation coefficients for the dynamic and synkinesis scores were 0.77 (r < 0.0001) and -0.78 (r < 0.0001), respectively. CONCLUSIONS AND RELEVANCE: There is moderately good agreement between the Sunnybrook FGS and the eFACE. Given the ease of using the eFACE on mobile devices, as well as its additional functionality, it may represent a reasonable facial grading option across disciplines in the future. LEVEL OF EVIDENCE: NA.

Comprehensive facial rehabilitation improves function in people with facial paralysis: a 5-year experience at the Massachusetts Eye and Ear Infirmary.

BACKGROUND: The Facial Grading Scale (FGS) is a quantitative instrument used to evaluate facial function after facial nerve injury. However, quantitative improvements in function after facial rehabilitation in people with chronic facial paralysis have not been shown. OBJECTIVE: The objectives of this study were to use the FGS in a large series of consecutive subjects with facial paralysis to quantitatively evaluate improvements in facial function after facial nerve rehabilitation and to describe the management of chronic facial paralysis. DESIGN: The study was a retrospective review. METHODS: A total of 303 individuals with facial paralysis were evaluated by 1 physical therapist at a tertiary care facial nerve center during a 5-year period. Facial rehabilitation included education, neuromuscular training, massage, meditation-relaxation, and an individualized home program. After 2 months of home exercises, the participants were re-evaluated, and the home program was tailored as necessary. All participants were evaluated with the FGS before the initiation of facial rehabilitation, and 160 participants were re-evaluated after receiving treatment. All participants underwent the initial evaluation at least 4 months after the onset of facial paralysis; for 49 participants, the evaluation took place more than 3 years after onset. RESULTS: Statistically significant increases in FGS scores were seen after treatment (P<.001, t test). The average initial score was 56 (SD=21, range=13-98), and the average score after treatment was 70 (SD=18, range=25-100). LIMITATIONS: A limitation of this study was that evaluations were performed by only 1 therapist. CONCLUSIONS: For 160 patients with facial paralysis, statistically significant improvements after facial rehabilitation were shown; the improvements appeared to be long lasting with continued treatment. The improvements in the FGS scores indicated that patients can successfully manage symptoms with rehabilitation and underscored the importance of specialized therapy in the management of facial paralysis.

Effects of modest testosterone supplementation and exercise for 12 weeks on body composition and quality of life in elderly men.

OBJECTIVE: One of the factors that may promote deterioration in quality of life and body composition in elderly men is the relative decline in serum testosterone levels with aging. In this study, we assessed the effects of modest doses of testosterone and a home-based strengthening program on quality of life and body composition in elderly men with relative testosterone insufficiency. DESIGN: Double-blind, placebo-controlled randomized study (testosterone), and additional randomization to a resistance exercise program or no additional exercise for 12 weeks in men between ages of 65 and 85 years with relative testosterone insufficiency. METHODS: Seventy sedentary, community dwelling men were randomized to a 5 mg testoderm transdermal system applied daily vs placebo system, and additionally randomized to a home-based resistance exercise program. Subjects were randomized to Group 1 (testosterone plus exercise), Group 2 (testosterone plus no exercise), Group 3 (placebo plus exercise), and Group 4 (placebo plus no exercise). Endpoints included quality of life (assessed by the short form-36 questionnaire) and body composition (measured by dual x-ray absorptiometry scan). RESULTS: Serum testosterone increased by a mean of 10.0 +/- 1.9, 6.6 +/- 1.6, 0.52 +/- 0.6, and 0.5 +/- 0.6 nmol/l in Groups 1, 2, 3, and 4 respectively. There was a significant interaction of testosterone and exercise on quality of life in the domains of physical functioning (P = 0.03), role physical (P = 0.01), general health (P = 0.049), and social functioning (P = 0.04). There were no effects of testosterone or exercise on quality of life alone, nor in body composition parameters. CONCLUSIONS: Modest testosterone supplementation to elderly men with relative testosterone insufficiency improved quality of life when accompanied by an exercise program. The combination of testosterone and exercise may be an important strategy in the elderly, though further studies are necessary to determine the long-term impact on body composition and function and for analysis of risk/benefit ratios as well.

Multimodality approach to management of the paralyzed face.

OBJECTIVES: Despite the ability of facial reanimation techniques to introduce meaningful movement to the paralyzed face, dynamic methods do not address all zones of the face. Our objective was to retrospectively review outcomes after multimodality management of the patient with facial paralysis, to describe several novel surgical methods that introduce subtle improvements in static facial balance, and to present an algorithm for comprehensive management of the paralyzed face. METHODS/RESULTS: Three hundred thirty-seven patients with facial paralysis were seen and treated in a busy facial nerve center setting over a 3-year period using a range of standard muscle transfers, physical therapy, chemodenervation with botulinum toxin, and static surgical techniques. Three adjunct techniques emerged as novel and useful procedures that more fully addressed facial balance issues than existing techniques. Of patients proceeding with physical therapy, greater than 80% of patients experienced a benefit, and 97% of those who proceeded with botulinum toxin therapy experienced a benefit. CONCLUSIONS: Facial paralysis is best managed using a multimodality approach that includes surgical interventions, physical therapy, and chemodeneveration. We describe three adjunctive surgical techniques for management of the paralyzed face and present a comprehensive algorithm for management of the paralyzed face. That may provide improved function and cosmesis in all zones of the paralyzed face.

Fluoxetine for vestibular dysfunction and anxiety: a prospective pilot study.

Anxiety states and disorders amplify the symptoms and impairment associated with vestibular dysfunction. Five patients with inner ear vestibular dysfunction and anxiety were prospectively treated with fluoxetine, 20-60 mg/day, and received an extensive battery of assessments at baseline and after 12 weeks of treatment. Fluoxetine led to significant or near significant reductions in anxiety measures and in impairment due to dizziness; improvements in clinical balance function and vestibular function were less clear. The data add to the literature suggesting a role for selective serotonin reuptake inhibitors in the treatment of dizziness and anxiety.

Vestibular rehabilitation: useful but not universally so.

OBJECTIVE: Although vestibular rehabilitation (VR) is gaining popularity, few data support its utility in improving locomotor stability, and no good predictors exist of whom will benefit most. STUDY DESIGN AND SETTING: A double-blind, placebo-controlled randomized trial of vestibular rehabilitation was conducted at a large tertiary care hospital on 124 patients (59 +/- 18 years old) with unilateral (n = 51) or bilateral (n = 73) vestibular hypofunction, of whom 86 completed a 12-week intervention. Of these 86, 27 returned for long-term (1-year) follow-up testing. The primary outcome measure was locomotor stability. RESULTS: Group A (6 weeks of VR) significantly (P < 0.01) increased their gait velocity and stability compared with group B (6 weeks of strengthening exercise), but there was a smaller difference (P = 0.05) between groups at 12 weeks, when both had had VR; there were no group differences at 1 year. Of the 86 who completed the intervention, 52 (61%) had clear locomotor gains. CONCLUSION AND SIGNIFICANCE: VR is helpful for most patients in providing locomotor stability, but further work is needed to determine the factors that prevent VR from being effective for all patients with vestibulopathy.